Previous work has shown that bradykinin (BK) interacts with B-2 type receptors in human fibroblasts and initiates a series of biochemical events resulting in increased phospholipase activity, release of arachidonate and formation of prostaglandins predominantly via the cyclooxygenase pathway. These prostaglandins, in turn, activate adenyl cyclase and increase cAMP content. The effects of BK on fibroblast cAMP content can be inhibited by the cyclooxygenase inhibitor indomethacin. BK also interacts with neuroblastoma cells and rapidly produces a marked and transient rise and fall in cAMP content. Analog potency suggests that the receptor is also of the B-2 type. In control to human fibroblasts, BK effects on cGMP content are not inhibited by indomethacin, but are inhibited by ETYA, an inhibition of lipoxygenase. These finding suggest that effects of BK on neuroblastoma cGMP content are perhaps mediated by lipoxygenase metabolites. In human fibroblasts various factors alter responsiveness to BK. Incubation with pertussis toxin for 24 hrs enhanced BK-stimulated prostaglandin formation, as did other agents (including cholera toxin) that increased fibroblast cAMP content. The response to 8-Br cAMP was biphasic. During initial stages of incubation with 8-Br-cAMP, BK stimulation of prostaglandin formation was reduced. Longer incubations with 8-Br cAMP or 8-Br-cGMP (which did not reduce BK responsiveness) enhanced the effect of BK on prostaglandin formation. These findings support the hypothesis that cyclic nucleotides can modulate BK-stimulation of prostaglandin formation.